The present invention relates to new compounds having a lanthanide and a tridentate ligand, a process for their preparation and their use in particular as polymerization catalysts.
The use of the lanthanide derivatives as catalysts for polymerization and copolymerization of olefines (Gibson et al., Angew. Chem., Int. Ed. Engl., (1999) 38, 428) and heterocycles (Yao et al., J. Polymer. Sci. Part A: Polymer Chem., (1996) 34, 1799) is known.
However, it has been shown that each type of catalyst used for polymerizations or copolymerizations produces respectively different polymers or copolymers in particular because of transesterification reactions which lead to inversions of the stereogenic centres (Jedlinski et al., Macromolecules, (1990) 191, 2287; Munson et al., Macromolecules, (1996) 29, 8844; Montaudo et al., Macromolecules, (1996) 29, 6461). The problem is therefore to find new catalytic systems in order to obtain new polymers or copolymers, and more particularly block copolymers. The use of catalytic systems making it possible to obtain block copolymers, allows control of the chain formation of the monomers in order to obtain specific copolymers having the appropriate properties. This is particularly useful for biocompatible copolymers, the biodegradation of which is influenced by this chain formation.
Therefore a subject of the invention is the products of general formula 1 
in which
M represents a lanthanide;
RM represents the hydrogen atom, a halogen atom or an alkyl, cycloalkyl, aryl, alkoxy, cycloalkoxy, aryloxy, alkylthio, cycloalkylthio, arylthio, amino, alkylamino, dialkylamino, cycloalkylamino, di(cycloalkyl)amino, alkyl(cycloalkyl)amino, arylamino, diarylamino, alkylarylamino or (cycloalkyl)arylamino radical;
A and B represent, independently, a carbon chain with 2 to 4 carbon atoms, optionally substituted by one of the following substituted (by one or more identical or different substituents) or non-substituted alkyl, cycloalkyl or aryl radicals, in which said substituent is a halogen atom, the alkyl, nitro or cyano radical;
L1, L2 and L3 represent, independently, a group of formula xe2x80x94E15(R15)xe2x80x94 in which E15 is an element of group 15 and R15 represents the hydrogen atom; one of the following substituted (by one or more identical or different substituents) or non-substituted alkyl, cycloalkyl or aryl radicals, in which said substituent is a halogen atom, the alkyl, nitro or cyano radical; a radical of formula xe2x80x94E14RRxe2x80x2Rxe2x80x3 in which E14 is an element of group 14 and R, Rxe2x80x2 and Rxe2x80x3 represent, independently, the hydrogen atom or one of the following substituted (by one or more identical or different substituents) or non-substituted alkyl, cycloalkyl, aryl, alkoxy, cycloalkoxy, aryloxy, alkylthio, cycloalkylthio or arylthio radicals in which said substituent is a halogen atom, the alkyl, nitro or cyano radical; or a radical of formula xe2x80x94SO2Rxe2x80x215 in which Rxe2x80x215 represents a halogen atom, an alkyl, haloalkyl or aryl radical optionally substituted by one or more substituents chosen from the alkyl, haloalkyl and halogen radicals.
In the definitions indicated above, the expression halogen represents a fluorine, chlorine, bromine or iodine atom, preferably chlorine. The expression alkyl preferably represents a linear or branched alkyl radical having 1 to 6 carbon atoms and in particular an alkyl radical having 1 to 4 carbon atoms such as the methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl and tert-butyl radicals.
The term haloalkyl preferably designates radicals in which the alkyl radical is as defined above and is substituted by one or more halogen atoms as defined above such as, for example, bromoethyl, trifluoromethyl, trifluoroethyl or also pentafluoroethyl. The alkoxy radicals can correspond to radicals in which the alkyl radical is as defined above. The methoxy, ethoxy, isopropyloxy or tert-butyloxy radicals are preferred. The alkylthio radicals preferably represent radicals in which the alkyl radical is as defined above such as, for example, methylthio or ethylthio. The alkylamino and dialkylamino radicals preferably represent radicals in which the alkyl radical is as defined above such as, for example, methylamino or dimethylamino.
The cycloalkyl radicals are chosen from the saturated or unsaturated monocyclic cycloalkyls. The saturated monocyclic cycloalkyl radicals can be chosen from radicals having 3 to 7 carbon atoms such as the cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl radicals. The unsaturated cycloalkyl radicals can be chosen from the cyclobutene, cyclopentene, cyclohexene, cyclopentadiene or cyclohexadiene radicals. The cycloalkoxy radicals can correspond to radicals in which the cycloalkyl radical is as defined above. The cyclopropyloxy, cyclopentyloxy or cyclohexyloxy radicals are preferred. The cycloalkylthio radicals can correspond to radicals in which the cycloalkyl radical is as defined above, such as for example cyclohexylthio. The cycloalkylamino and di(cycloalkyl)amino radicals can correspond to radicals in which the cycloalkyl radical is as defined above such as for example cyclohexylamino and di(cyclohexyl)amino.
The aryl radicals can be of mono or polycyclic type. The monocyclic aryl radicals can be chosen from the phenyl radicals optionally substituted by one or more alkyl radicals, such as tolyl, xylyl, mesityl, cumenyl. The polycyclic aryl radicals can be chosen from the naphthyl, anthryl, phenanthryl radicals. The aryloxy radicals can correspond to radicals in which the aryl radical is as defined above. The phenoxy, 2,4,6-tritertiobutylphenoxy, tolyloxy or mesityloxy radicals are preferred. The arylthio radicals preferably designate radicals in which the aryl radical is as defined above such as for example in phenylthio. The arylamino and diarylamino radicals preferably designate radicals in which the aryl radical is as defined above such as, for example, phenylamino or diphenylamino.
The alkyl(cycloalkyl)amino radicals can correspond to radicals in which the alkyl and cycloalkyl radicals are as defined above such as, for example methyl(cyclohexyl)amino. The alkylarylamino radicals preferably designate radicals in which the alkyl and aryl radicals are as defined above such as, for example methylphenylamino. The (cycloalkyl)arylamino radicals can correspond to radicals in which the cycloalkyl and aryl radicals are as defined above such as, for example (cyclohexyl)phenylamino.
The compounds of formula 1 can be presented in the form of a monomer or of a dimer and more particularly the compounds of formula 1 in which M represents a samarium atom are generally presented in the form of a dimer.
A more particular subject of the invention is the products of general formula 1 as defined above, characterized in that RM represents a halogen atom; A and B represent, independently, a carbon chain with 2 to 4 carbon atoms; L1, L2 and L3 represent, independently, a radical of formula xe2x80x94E15(R15)xe2x80x94 in which E15 is a nitrogen or phosphorus atom and R15 represents an alkyl radical or a radical of formula xe2x80x94E14RRxe2x80x2Rxe2x80x3 in which E14 represents a carbon or silicon atom and R, Rxe2x80x2 and Rxe2x80x3 represent, independently, the hydrogen atom or an alkyl radical.
Preferably, M represents a samarium atom. Preferably also, RM represents a chlorine atom; A and B represent, independently, a carbon chain with 2 carbon atoms; L1, L2 and L3 represent, independently, a radical of formula xe2x80x94E15(R15)xe2x80x94 in which E15 is a nitrogen atom and R15 represents a methyl, ethyl, propyl, isopropyl radical or a radical of formula xe2x80x94E14RRxe2x80x2Rxe2x80x3 in which E14 represents a silicon atom and R, Rxe2x80x2 and Rxe2x80x3 represent, independently, the hydrogen atom or a methyl, ethyl, propyl or isopropyl radical.
A more particular subject of the invention is the product described hereafter in the examples, in particular the product corresponding to the following formula:
xe2x80x94[(Me3SiNCH2CH2)2NMe]SmCl.
A subject of the invention is also a process for the preparation of the products of general formula 1 as defined above, characterized in that a product of formula I
(L1xe2x80x94Axe2x80x94L3xe2x80x94Bxe2x80x94L2)2xe2x88x92, 2Y+xe2x80x83xe2x80x83(I)
in which L1, A, L3, B and L2 have the meanings indicated above and Y represents the hydrogen atom, a metal or an organometallic group, is reacted with a product of formula II
MRMZ1Z2xe2x80x83xe2x80x83(II)
in which M and RM have the meanings indicated above and Z1 and Z2 represent, independently, a parting group, in order to obtain a product of formula I as defined above.
The reaction of a compound of general formula I with a compound of general formula II in order to obtain a compound of general formula 1, can be carried out under an inert atmosphere such as under a freon or argon atmosphere, in an aprotic solvent, at a temperature comprised between xe2x88x9290 and +50xc2x0 C. The compounds I thus obtained are purified by standard purification methods.
As aprotic solvent, the aromatic hydrocarbons such as benzene, toluene; the aliphatic hydrocarbons such as pentane, heptane, hexane, cyclohexane; ethers such as diethylether, dioxane, tetrahydrofuran or ethyltertiobutyl ether can be used.
The compounds of formula 1 can comprise one or more coordinating solvent molecules used during the preparation process. The expression coordinating solvent represents an aromatic hydrocarbon such as benzene, toluene; a cyclic or acyclic dialkyl ether such as diethylether, dioxane, tetrahydrofuran, ethylterbutylether; a chlorinated solvent such as dichloromethane, chloroform; an aliphatic or aromatic nitrile such as acetonitrile, benzonitrile; an aliphatic or aromatic, cyclic or acyclic ketone such as acetone, acetophenone, cyclohexanone; an aliphatic or aromatic, cyclic or acyclic carboxylic acid derivative, such as ethyl acetate or dimethylformamide.
In compounds I, Y represents the hydrogen atom, a metal or a metallic group. The metallic group can be a compound of formula Rxe2x80x2xe2x80x3M1 or Rxe2x80x2xe2x80x33M2 in which Rxe2x80x2xe2x80x3 represents a halogen atom or indifferently an alkyl, cycloalkyl, aryl, alkoxy, cycloalkoxy or aryloxy radical as previously defined, M1 is an alkaline-earth such as magnesium or a zinc or mercury atom and M2 a tin or lead atom; preferably, the metallic group is chosen from the MgBr, ZnMe, SnMe3, SnBu3 or PbMe3 groups. The metal can be an alkali metal chosen from lithium, sodium or potassium.
In compounds II, Z1 and Z2 represent, independently, a parting group such as a halogen atom, an alkyl, cycloalkyl, alkoxy, aryl or aryloxy group as previously defined, or also a methanesulphonyloxy, a benzenesulphonyloxy, p-toluenesulphonyloxy.
The starting products of formula I are known products or can be prepared from known products. For their synthesis, the following references can be mentioned: Cloke et al., J. Chem. Soc., Dalton Trans. (1995) 25; Wilkinson and Stone, Comprehensive Organometallic Chemistry (1982) vol. 1, 557.
The products of formula II are commercially available or can be manufactured by methods known to a person skilled in the art.
A subject of the invention is also the use of the products of formula 1 as defined above, as catalysts for carrying out (co)polymerization, that is to say polymerization or copolymerization. Whilst carrying out (co)polymerization, the compounds according to the invention also play the role of chain initiator and/or regulator.
The compounds of formula 1 are particularly useful for carrying out the polymerization of heterocycles. The heterocycles can contain one or more heteroatoms of groups 15 and/or 16, and are from three to eight members in size. As an example of heterocycles corresponding to the aforementioned formulation, epoxides, thioepoxides, cyclic esters or thioesters such as the lactones, the lactames and the anhydrides can be mentioned.
The compounds of formula 1 are also particularly useful for carrying out the (co)polymerization of cyclic esters. As an example of cyclic esters, the polymer cyclic esters of lactic and/or glycolic acid can be mentioned. Random or block copolymers can be obtained depending on whether monomers are introduced together at the start of the reaction, or sequentially during the reaction.
A subject of the invention is also a process for the preparation of random or block copolymers or polymers, which consists of bringing a polymerization catalyst and optionally a polymerization solvent into contact with one or more monomers, a chain initiator and/or regulator, the said process characterized in that the chain initiator and/or the regulator and the polymerization catalyst are represented by the same compound which is chosen from the compounds of formula (1) as defined above.
The (co)polymerization can be carried out either in solution or in supercooling. When the (co)polymerization is carried out in solution, the reaction solvent can be the (or one of the) substrate(s) used in the catalytic reaction. Solvents which do not interfere with the catalytic reaction itself are also suitable. As an example of such solvents, saturated or aromatic hydrocarbons, ethers, aliphatic or aromatic halides can be mentioned.
The reactions are carried out at temperatures comprised between ambient temperature and approximately 250xc2x0 C.; the temperature range comprised between 40 and 200xc2x0 C. proves most advantageous. The durations of the reactions are comprised between a few minutes and 300 hours, and preferably between 5 minutes and 72 hours.
This (co)polymerization process is particularly suitable for obtaining a (co)polymer of cyclic esters, in particular the polymer cyclic esters of lactic and/or glycolic acid. The products obtained such as biodegradable lactic, glycolic, copolymer are advantageously used as a support in sustained release therapeutic compositions. The process is also particularly suitable for the polymerization of epoxides, in particular propene oxide. The polymers obtained are compounds which can be used for the synthesis of organic liquid crystals or also as semi-permeable membranes.
The invention also relates to polymers or copolymers which can obtained by carrying out a process such as described above. The polydispersity (Mw/Mn) of the (co)polymers thus obtained can be modified by leaving the reaction mixture at the reaction temperature after total conversion of the monomer(s). The masses of the (co)polymers are little affected during this process. These phenomenon are due to the inter- or intra-molecular transesterification reactions (Kiecheldorf et al., Macromolecules, (1988) 21, 286).